- In situ generation of nitrile oxides from copper carbene and tert -butyl nitrite: Synthesis of fully substituted isoxazoles
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Herein, we present a novel [3 + 2] cycloaddition reaction of β-keto esters with nitrile oxides, which were generated in situ from copper carbene and tert-butyl nitrite. This three-component reaction provides new methodology for the direct synthesis of fully substituted isoxazole derivatives, featuring mild reaction conditions, readily accessible starting materials and simple operation. The experimental studies and DFT calculations suggest that the reaction starts with the generation of the key intermediate nitrile oxides, followed by a [3 + 2] cycloaddition reaction of β-keto esters to give the final isoxazole products.
- Chen, Rongxiang,Ogunlana, Abosede Adejoke,Fang, Shangwen,Long, Wenhao,Sun, Hongmei,Bao, Xiaoguang,Wan, Xiaobing
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- Analyse structurale des derives fonctionnels des acides carboxyliques Partie III. Acetate d'ethyle et derives α-halogenes
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Methylene bending mode analysis of ethyl esters of acetic and haloacetic acids XCH2CO2C2H5 where X=H(I), F(II), Cl(III), Br(IV) and I(V) reveals that in the dissolved state (CCl4) these compounds have conformations induced by rotating motion of the XCH2 and C2H5 groups ( (II), (III) and (IV) ) or by C2H5 group rotation exclusively ( (I) and (V) ).In the last case, (I) exists in gauche and anti conformations while (V) occurs in gauche-gauche and gauche-anti conformations.A theoretical study of compounds (I), (II) and (III) by the PCILO method and Onsager formalism leads to the following conclusions.The conformers of (I) have a dihedral angle (H3)C-C(H2)-O-C of 70 deg (gauche conformer) and 180 deg (anti conformer).For (II) and (III), there are four stable conformers whose dihedral angles φ3=(H3)C-C(H2)-O-C and θ=X-C-C=O values are in agreement with C2H5 and CH2X group orientations found in experimental analysis.
- Maury, Catherine,Petrissans, Jean
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- Activation of alkyl halides via a silver-catalyzed carbene insertion process
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The silver complex [HB(3,5-(CF3)2Pz)3]Ag(THF) featuring a highly fluorinated tris(pyrazolyl)borate ligand catalyzes the formation of aliphatic carbon-halogen bond activation products under remarkably mild conditions. For example, the reaction between CHCl3 and ethyl diazoacetate (EDA) at room temperature in the presence of the silver catalyst afforded HClC(CO2Et)CCl2H in 60% yield. The presence of β-hydrogens on the alkyl halide leads to net hydrogen halide addition to the carbene and an alkene. Copyright
- Dias, H. V. Rasika,Browning, R. Greg,Polach, Sharon A.,Diyabalanage, Himashinie V. K.,Lovely, Carl J.
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- A method for esterification reaction rate prediction of aliphatic monocarboxylic acids with primary alcohols in 1,4-dioxane based on two parametrical taft equation
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Esterification reaction rates of aliphatic monocarboxylic acids with primary alcohols in 1,4-dioxane as inert solvent were investigated. Acids were esterified with 1-propanol and alcohols with acetic acid as model reactants at a constant temperature of 60°C, at a fixed ionic strength and pH in a batch reactor with a constant volume. For evaluation of reaction rates, an exact kinetic equation for the equilibrium reaction was applied. Under these conditions and for low reactants, concentrations reaction rate depends only on the structure of reactants and, therefore, can be predicted by a correlation equation with two Taft coefficients (inductive and steric effects). From these equations, it is possible to estimate the esterification reaction rate constant for other acid-alcohol pairs. This methodology may also be suitable for other kinetic systems measured under comparable experimental conditions.
- Vojtko, Jan,Tomcik, Peter
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- Visible-Light-Assisted Gold-Catalyzed Fluoroarylation of Allenoates
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A strategically novel synthetic method for the fluoroarylation of allenic ester was developed that enables the expedient construction of a host of β-fluoroalkyl-containing cinnamate derivatives. The reaction proceeds through visible-light-promoted gold redox catalysis, occurs smoothly under very mild reaction conditions, accommodates a large variety of functional groups, and more importantly allows the incorporation of fluorine and aryl groups with excellent regio- and stereoselectivity. The concomitant activation mode for both the allene motif and the hydrogen fluoride is key for the success of the reaction.
- Feng, Chao,Tang, Hai-Jun,Zhang, Xinggui,Zhang, Yu-Feng
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- In Situ Generation of Oxazole Ylide and Interception with Sulfonamide: Construction of Amidines Using Two Diazo Molecules
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A novel generation of oxazole ylide and interception with sulfonamide have been well developed to construct fully substituted amidines. This copper-catalyzed four-component reaction incorporates two diazo molecules to target amidines and shows broad substrate scope, excellent functional groups tolerance and good to excellent yields.
- Chen, Jijun,Long, Wenhao,Zhao, Yanwei,Li, Haiyan,Zheng, Yonggao,Lian, Pengcheng,Wan, Xiaobing
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- Facile One Pot Multi-Component Solvent-Free Synthesis of 2,4,5-Trisubstituted Imidazoles Using “Green” and Expeditious Ionic Liquid Catalyst under Microwave Irradiation
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Acetic acid functionalized poly(4-vinylpyridinium) bromide is a highly efficient and recyclable catalyst for the construction of 2,4,5-trisubstituted imidazole derivatives by a three-component condensation of benzyl with various aldehydes and ammonium acetate under solvent free conditions. The microwave initiated process leads to analytically pure compounds within 2–5 min. The advantages of this “green” methodology are cost-effectiveness, simple procedure, low energy consumption, no involvement of organic solvents, safe operation, clean reaction profile, high yields, and recyclability of the catalyst.
- Sonyanaik,Ashok,Rambabu,Ravi,Kurumanna,Madhu,Sakram
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- Synthesis process of thiazole medical intermediate
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The invention discloses a synthesis process of thiazole medical intermediate.The synthesis process comprises the following steps: step 1, mixing ethyl pyruvate and dichloromethane of which the volume is 2 times that of the ethyl pyruvate at room temperature, adding an obtained mixture into a reactor, starting stirring, and keeping the temperature of a system at about 20 DEG C; step 2, starting to dropwise add a dichloromethane solution of bromine, controlling the temperature to enable the system to be about 20-30 DEG C, sealing the reactor, and introducing a strong alkali solution to absorb acid gas HBr; and step 3, after dropwise adding is completed, closing a cold well, performing stirring at normal temperature for about 2 hours until the color of the reaction liquid gradually becomes light yellow to light brown, monitoring that no raw material exists through TLC, and concentrating the obtained reaction liquid. According to the synthesis process of the thiazole medical intermediate, by introducing the defoaming agent n-hexane, generated gas foam can be quickly dissolved out and released from the solvent, and the phenomenon of one-time flushing is avoided; and by introducing the n-hexane solvent, solids can be effectively separated out at low temperature, the impurity content can be controlled to be about 1%, the purification difficulty is greatly reduced, and crystallization is facilitated.
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Paragraph 0013
(2021/06/09)
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- Acridine Orange Hemi(Zinc Chloride) Salt as a Lewis Acid-Photoredox Hybrid Catalyst for the Generation of α-Carbonyl Radicals
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A readily accessible organic-inorganic hybrid catalyst is reported for the reductive fragmentation of α-halocarbonyl compounds. The robust hybrid catalyst is a self-stabilizing combination of ZnCl2 Lewis acid and acridine orange as the photoactive organic dye. Mechanistic specifics of this hybrid catalyst have been studied in detail using both photophysical and electrochemical experiments. A systematic study enabled the discovery of the appropriate Lewis acid for the effective LUMO stabilization of α-halocarbonyl compounds and thereby lowering of reduction potential within the range of a standard organic dye. This strategy resolves the issues like dehalogenative hydrogenation or homo-coupling of alkyl radicals by guiding the photoredox cycle through an oxidative quenching pathway. The cooperativity between the photoactive organic dye and the Lewis acid counterparts empowers functionalization with a wide range of coupling partners through efficient and controlled generation of alkyl radicals and serves as an appropriate alternative to the expensive late transition metal-based photocatalysts. To demonstrate the application potential of this cooperative catalytic system, four different synthetic transformations of α-carbonyl bromides were explored with broad substrate scopes.
- Das, Sanju,De Sarkar, Suman,Mandal, Tanumoy
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supporting information
(2021/12/10)
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- Synthesis, antiinflammatory activity, and molecular docking studies of bisphosphonic esters as potential MMP-8 and MMP-9 inhibitors
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Bisphosphonic acids (or bisphosphonates) have been successfully used in the clinic treatment of bone diseases for over decades. Additionally, the antiinflammatory activity of these compounds has been gaining attention. In our previous work, we synthesized and in vivo evaluated the bisphosphonic esters 1 and 2, finding a moderate edema inhibition upon oral and topical administration on BALB/c mice. Thus, in this work, the bioisosteric replacement of an amide functional group for an ester afforded the new bisphosphonates 3–6, which had a moderate oral edema inhibition (25 mg/kg dose) and a significant topical antiinflammatory activity (2 mg/ear) on BALB/c mice, with 6 being the most active hit (55.9% edema inhibition), comparable to the positive control (55.5% edema inhibition) on a TPA topical model. Next, to assess the acute toxicity of the synthesized derivatives, test animals were administered with 50–100 mg/kg of 3–6, respectively, by an oral route, and after 14 days, neither lethality nor a significative weight loss were observed. Finally, a structure–activity relationship (SAR) and a molecular docking analysis of 3–6 helped us to explain the trend observed in biological tests. Considering all these aspects, we propose the inhibition of MMP-8 and MMP-9 as a possible action mechanism of the synthesized derivatives.
- Cortes-Pacheco, Abimelek,Jiménez-Arellanes, María Adelina,Juárez-Vázquez, María del Carmen,López-Torres, Adolfo,Palacios-Can, Francisco José,Ramírez-Marroquín, Oscar Abelardo,Razo-Hernández, Rodrigo Said,Valcarcel-Gami?o, José Antonio
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supporting information
p. 1277 - 1287
(2020/07/10)
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- Cross coupling of sulfonyl radicals with silver-based carbenes: A simple approach to β-carbonyl arylsulfones
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A coupling reaction between sulfonyl radicals and silver-based carbenes has been well established. This simple radical-carbene coupling (RCC) process provided an efficient approach to a variety of β-carbonyl arylsulfones from sodium arylsulfinates and diazo compounds, and was characterized by wide substrate scope, easy scale-up, simple manipulation, accessible starting materials, and mild reaction conditions.
- Li, Jingjing,Lian, Pengcheng,Wan, Xiaobing,Wang, Hanghang,Zheng, Yonggao
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supporting information
p. 2163 - 2169
(2020/03/27)
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- Synthesis method of ethyl 3-hydroxyhexanoate
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The invention discloses a synthesis method of ethyl 3-hydroxyhexanoate. The method is characterized by comprising the following steps: reacting bromine with acetic acid to prepare bromoacetic acid; reacting the bromoacetic acid with ethanol in the presence of sulfuric acid to generate ethyl bromoacetate; adding 500kg of dichloromethane and 140kg of n-butyraldehyde into a reaction kettle; adding acatalyst, heating to reflux, dropwise adding 250kg of the ethyl bromoacetate serving as a product obtained in the previous step, controlling the dropwise adding speed, controlling the adding to be completed within 3 hours in a reflux state, preserving heat for 2 hours, cooling to room temperature, washing to neutrality, transferring into a rectifying tower, and rectifying to obtain a qualified product, namely the ethyl 3-hydroxyhexanoate.
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Paragraph 0017; 0019; 0021; 0023; 0025; 0027; 0029; 0031
(2020/02/27)
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- Sulfinate-Engaged Nucleophilic Addition Induced Allylic Alkylation of Allenoates
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A strategically novel Pd-catalyzed nucleophilic addition induced allylic alkylation reaction (NAAA) of allenoates has been successfully accomplished. By judiciously integrating ZnCl2-promoted Michael addition with Pd-catalyzed allylic alkylation, allenoates readily undergo allyl-sunfonylation at the internal double bond, thus providing a straightforward avenue for the rapid assembly of a host of structurally diversified α-allyl-β-sufonylbut-3-enoate derivatives. The success of this transformation profits from a delicate control of the reaction kinetic of each elementary step, thanks to the synergistic interaction of Pd/Zn bimetallic system, thus suppressing either direct allylic sulfonylation or premature quenching of therein in situ generated ester enolate intermediate. Furthermore, by expanding the scope of workable Michael acceptor beyond those previously required doubly activated ones, such as methylenemalononitrile, the present work substantially enriches the repertoire of NAAA reactions.
- Lin, Ling-Zhi,Che, Yuan-Yuan,Bai, Peng-Bo,Feng, Chao
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supporting information
p. 7424 - 7429
(2019/10/02)
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- Interception of Secondary Amide Ylide with Sulfonamides: Catalyst-Controlled Synthesis of N-Sulfonylamidine Derivatives
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A novel, secondary amide activation strategy has been developed through the in situ generation of ylides from amides and diazoacetates. Under the developed reaction conditions, Mn-catalyzed ylide formation and interception reaction by sulfonamide delivered a variety of N-sulfonylamidines. Notably, when highly active Zn(OTf)2 was used as the catalyst, further N-H insertion products were obtained. In contrast with traditional methods, our amide activation strategy is distinguished by accessible starting material, inexpensive catalyst, and broad substrate scope.
- Chen, Jijun,Long, Wenhao,Yang, Yonggang,Wan, Xiaobing
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supporting information
p. 2663 - 2666
(2018/05/22)
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- Regio- and Stereoselective Nickel-Catalyzed Coupling of Boronic Acids with Allenoates
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The Ni(II)-catalyzed cross-coupling of arylboronic acids with allenoates is documented. The high regio- and stereoselectivity of the process enables a wide range of β-aryl β,γ-unsaturated esters to be prepared in good to excellent yields (up to 95%) and high E / Z -selectivity. Additionally, [3+2]-cascade sequence was observed when 2-formylphenylboronic acid was employed.
- Liu, Yang,Daka, Mario,Bandini, Marco
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p. 3187 - 3196
(2018/08/17)
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- Interception of Radicals by Molecular Oxygen and Diazo Compounds: Direct Synthesis of Oxalate Esters Using Visible-Light Catalysis
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The synthesis of oxalate esters through a radical process, rather than the traditional ionic reaction, has been well developed in which the radicals induced by visible light are trapped by molecular oxygen and diazo compounds under room temperature. This reaction is operationally simple, mild, and shows broad substrate scopes in α-bromo ketones and diazo compounds.
- Ma, Meihua,Hao, Weiwei,Ma, Liang,Zheng, Yonggao,Lian, Pengcheng,Wan, Xiaobing
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supporting information
p. 5799 - 5802
(2018/09/12)
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- Preparation method for 2,4-dichlorophenoxyacetic acid
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The invention provides a preparation method for 2,4-dichlorophenoxyacetic acid. The preparation method comprises the following steps: A) reacting C2 or above-C2 alcohol with halogenated acetic acid soas to obtain halogenated acetate; B) reacting halogenated acetic acid with 2,4-dichlorophenolate so as to obtain 2,4-dichlorophenoxyacetate; and C) hydrolyzing 2,4-dichlorophenoxyacetate so as to obtain 2,4-dichlorophenoxyacetic acid. According to the invention, C2 or above-C2 alcohol reacts with halogenated acetic acid to obtain a halogenated acetate intermediate, the intermediate has good stability, few reaction by-products are produced, and high yield is realized; then the intermediate further reacts with 2,4-dichlorophenolate to obtain 2,4-dichlorophenoxyacetate; and finally, 2,4-dichlorophenoxyacetate is hydrolyzed to obtain 2,4-dichlorophenoxyacetic acid. Through a specific reaction route of the invention, the finally prepared 2,4-dichlorophenoxyacetic acid has high purity and yield, few by-products are produced, the reaction route is simple, and the application of the preparation method is facilitated.
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Paragraph 0060; 0061
(2018/09/08)
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- Photoinduced Intermolecular [4+2] Cycloaddition Reaction for Construction of Benzobicyclo[2.2.2]octane Skeletons
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A novel and efficient method for the synthesis of highly substituted benzobicyclo[2.2.2]octane skeletons has been explored. Under UV-light irradiation, o-divinylbenzenes underwent a pericyclic reaction to form the cyclic o-quinodimethane intermediates which were subsequently reacted with olefins through [4+2] addition to construct the benzobicyclo[2.2.2]octane skeletons in mild conditions. Gram scale reactions demonstrated the synthetic potential application of this protocol.
- Liu, Qiang,Wang, Junlei,Li, Dazhi,Yang, Chao,Xia, Wujiong
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p. 1389 - 1402
(2017/02/10)
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- Cycloaddition of Fluorenone N-Aryl Nitrones with Methylenecyclopropanes and Sequential 1,3-Rearrangement: An Entry to Synthesis of Spirofluorenylpiperidin-4-ones
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A facile synthesis of various spirofluorenylpiperidin-4-ones has been achieved in good yields from fluorenone N-aryl nitrones and methylenecyclopropanes. This method involved an initial cycloaddition to form a 5-spirocyclopropane-isoxazoline, which underwent a highly selective 1,3-rearrangement to give the desired product. The stereochemistry of the spirofluorenylpiperidin-4-one could be controlled by the cycloaddition and sequential rearrangement strategy. Furthermore, the spirofluorenylpiperidin-4-ones could be not only prepared in one-pot procedure but also converted to useful scaffolds by reduction or oxidation conditions.
- Ma, Xiao-Pan,Zhu, Jie-Feng,Wu, Si-Yi,Chen, Chun-Hua,Zou, Ning,Liang, Cui,Su, Gui-Fa,Mo, Dong-Liang
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p. 502 - 511
(2017/04/26)
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- Phosphine-Catalyzed Domino β/γ-Additions of Benzofuranones with Allenoates: A Method for Unsymmetrical 3,3-Disubstituted Benzofuranones
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A phosphine-catalyzed domino process of benzofuranones with allenoates has been developed which furnishes highly functionalized unsymmetrical 3,3-disubstituted benzofuranones in synthetically useful yields. The mechanism for the transformation is a tandem β-umpolung/γ-umpolung process.
- Huang, Zhusheng,Yang, Xiuqin,Yang, Fulai,Lu, Tao,Zhou, Qingfa
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supporting information
p. 3524 - 3527
(2017/07/17)
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- Regio- and Stereoselective Copper(II)-Catalyzed Hydrosilylation of Activated Allenes in Water: Access to Vinylsilanes
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By using catalytic amounts of copper(II), 4-picoline, and dimethylphenylsilylpinacol borane, a series of allenoates were silylated on the β carbon in good to excellent yields and high (E)-selectivity. The mild and efficient silylation method is conducted in water under atmospheric conditions to afford vinylsilanes.
- Pashikanti, Srinath,Calderone, Joseph A.,Nguyen, Matthew K.,Sibley, Christopher D.,Santos, Webster L.
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supporting information
p. 2443 - 2446
(2016/06/09)
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- Synthesis and characterization of acetic acid functionalized poly (4-vinylpyridinium) salt as new catalyst for the synthesis of spiropyran derivatives and their biological activity
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Acetic acid functionalized poly(4-vinylpyridinium) bromide (APVPB), as a new and heterogeneous catalyst, was designed and successfully tested on the synthesis of 2-aminospiro[indoline-3,4?pyran]-2-one and spiro[indeno[1,2-b]quinoxaline-11,4-pyran]-2?-amine derivatives. Also, infrared spectroscopy (FT-IR), thermal gravimetric analysis (TGA), differential thermal gravimetric (DTG), scanning electron microscope (SEM), X-ray diffraction analysis (XRD) and energy dispersive X-ray analysis (EDX) of the catalyst has been studied in the presented work. The prepared spiro-pyrans were solved in DMSO and subjected to antioxidant activity screening by DPPH free radical scavenging assay and antifungal activity against Fusarium oxysporum. Results showed that the synthesized spiro-pyran possess strong antioxidant activity (IC50; 0.161 ± 0.009 to 1.509 ± 0.007 mg/ml) and also good inhibition activity against Fusarium oxysporum (65.8 ± 1.4% to 88.3 ± 2.2% at 500 ppm concentration and 89.2 ± 3.2% to 100 ± 0.0% at 1000 ppm concentration). For their biological activities, the prepared spiro-pyran compounds may be suggested to apply as alternative systems in medicine and agriculture.
- Moosavi-Zare, Ahmad Reza,Zolfigol, Mohammad Ali,Noroozizadeh, Ehsan,Zarei, Mahmoud,Karamian, Roya,Asadbegy, Mostafa
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p. 217 - 228
(2016/10/30)
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- One-Step Synthesis of Substituted Benzofurans from ortho- Alkenylphenols via Palladium-Catalyzed C=H Functionalization
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A dehydrogenative oxygenation of C(sp2)=H bonds with intramolecular phenolic hydroxy groups has been developed, which provides a straightforward and concise access to structurally diversely benzofurans from ortho-alkenylphenols. The reaction is catalyzed by palladium on carbon (Pd/C) without any oxidants and sacrificing hydrogen acceptors.
- Yang, Dejun,Zhu, Yifei,Yang, Na,Jiang, Qiangqiang,Liu, Renhua
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supporting information
p. 1731 - 1735
(2016/06/09)
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- Highly efficient preparation of selectively isotope cluster-labeled long chain fatty acids via two consecutive Csp3-Csp3 cross-coupling reactions
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An efficient synthesis involving two copper-catalyzed alkyl-alkyl coupling reactions has been designed to easily access doubly isotope-labeled fatty acids. Such NMR- and IR-active compounds were obtained in excellent overall yields and will be further used for determining the conformation of an alkyl chain of lipidic biomolecules upon interaction with proteins.
- Lethu, Sebastien,Matsuoka, Shigeru,Murata, Michio
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supporting information
p. 844 - 847
(2014/03/21)
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- Highly selective synthesis of α-bromoesters using molecular bromine catalyzed by phosphorus
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A series of α-bromoesters have been synthesized by applying Hell-Volhard-Zelinsky reaction catalyzed by phosphorus instead of usual phosphorus tribromide. An excellent regioselectivity to good yields are achieved at comparatively mild reaction conditions of an operational simplicity.
- Sun, Zhaoyun,Peng, Xinhua,Dong, Xiongzi,Shi, Wenwen
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scheme or table
p. 929 - 930
(2012/07/30)
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- Direct conversion of olefins into α-bromo ketones using O-iodoxybenzoic acid and tetraethylammonium bromide
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Utilizing full potential of IBX, a mild, selective, and facile method has been developed for the direct conversion of olefins into the corresponding α-bromo ketones by using 1.1 equivalents each of o-iodoxybenzoic acid and tetraethylammonium bromide. Georg Thieme Verlag Stuttgart - New York.
- Deshmukh, Swapnil S.,Chaudhari, Kiran H.,Akamanchi, Krishnacharya G.
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experimental part
p. 81 - 83
(2011/03/20)
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- Solvent-free synthesis of 2-amino-3-aryl-5-substituted thiophenes as anti-inflammatory agents using KF-Al2O3 under microwave irradiation
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The synthesis of 2-amino-3-aryl-5-substituted thiophenes as anti-inflammatory agents catalyzed by KF-Al2O3 under microwave irradiation is reported. Copyright Taylor & Francis Group, LLC.
- Saeidian, Hamdollah,Sadeghi, Azam,Mirjafary, Zohreh,Moghaddam, Firouz Matloubi
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p. 2043 - 2053
(2008/09/21)
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- Compounds for the management of aging-related and diabetic vascular complications, process for their preparation and therapeutic uses thereof
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Novel compounds of the pyridinium series useful for the management of diabetes and aging-related vascular and neurovascular complications, including kidney disease, nerve damage, atherosclerosis, retinopathy, inflammatory disorders, immunological disorders, oxidative stress, dermatological disorders and discoloration of teeth, by breaking preformed AGE, of the general formula I, or pharmaceutically acceptable salts thereof, wherein, R1, R2, R3, X and m are as defined in the specification. Also disclosed is a method for preparation of the compounds of general formula (I) and pharmaceutical composition containing one or more compounds as defined above as active ingredients. Also disclosed is a method of treatment of a diabetic patient by administering the compounds as defined above, either singly or in combination with drugs for antidiabetic therapy.
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- Preparation and Characterization of [5-13C]-(2S,4R)-Leucine and [4-13C]-(2S,3S)-Valine - Establishing Synthetic Schemes to Prepare Any Site-Directed Isotopomer of L-Leucine, L-Isoleucine and L-Valine
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In this paper a chemo-enzymatic method has been developed that gives access to any isotopomer of the essential amino acids isoleucine and valine. The method gives the correct introduction of the second chiral center in (2S,3S)-isoleucine and allows for discrimination between the two prochiral methyl groups in valine as shown by the preparation of (2S,3S)-[4- 13C] valine. For the preparation of (2S)-leucine in any isotopomeric form, the O'Donnell method to prepare optically active amino acids has been used. The protected glycine scaffold used in this method has been prepared by a strategy that allows access to any isotopomeric form. The preparation of [5-13C]-(2S,4R)-leucine shows that the O'Donnell method in combination with the Evans method to obtain chiral 2-methylpropyl iodide leads to a good discrimination between the two prochiral methyl groups. The O'Donnell strategy for the preparation of α-amino acids is preferred over other methods since the reaction conditions are mild, the chiral auxiliary can be easily recovered and the optically active product can be easily separated. For the preparation of isotopically enriched valine and isoleucine the O'Donnell method is not suitable, because the alkyl substituents involved have a secondary halide substituent which is sterically too hindered to give an effective reaction with the protected glycine. Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003.
- Siebum, Arjan H. G.,Woo, Wei Sein,Lugtenburg, Johan
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p. 4664 - 4678
(2007/10/03)
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- Bromoacetyl bromide: A versatile and selective cleaving agent for ethers and acetals
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It is shown that bromoacetyl bromide can be utilized for the selective cleavage of ethers and acetals in high yields. With cyclic ethers and acetals as starting materials, cleavage products are produced with two strategically positioned bromo substituents which may be exploited for selective extention of the carbon chain.
- Schneider, David F.,Viljoen, Murray S.
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p. 721 - 728
(2007/10/03)
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- Synthesis and spectroscopic characterization of [1′-14C]ubiquinone-2, [1′-14C]-5-demethoxy-5-hydroxyubiquinone-2, and [1′-14C]-5-demethoxyubiquinone-2
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[1′-14C]Ubiquinone-2, [1′-14C]-5-demethoxy-5-hydroxyubiquinone-2, and [1′-14C]-5-demethoxyubiquinone-2 have been synthesised from [1-14C]acetic acid. A common feature of these benzoquinones is the isoprenoid chain, and the 14C-label has therefore been incorporated in this isoprenoid. The coupling of the different quinone head groups and the isoprenoid chain is the last step in the total synthesis, to prevent unnecessary loss of the labelled material during synthesis. The products have been characterised by mass spectrometry, 1H NMR and 13C NMR.
- Van Der Klei, Anita,De Jong, Robertus L. P.,Lugtenburg, Johan,Tielens, Aloysius G. M.
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p. 3015 - 3023
(2007/10/03)
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- P38 MAP kinase inhibitors
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The present invention relates to compounds of Formula (I) that are p-38 MAP kinase inhibitors, pharmaceutical compositions containing them, methods for their use, and methods for preparing these compounds.
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- Azulene derivatives
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The invention provides novel azulene derivatives of general formula I wherein R1 to R6 have the significance given in the description, as well as their tautomers, enantiomers, diastereomers, racemates and physiologically compatible salts or esters and substances which are hydrolyzed or metabolized in vivo to compounds of formula I. The invention is also concerned with a process and intermediates for the manufacture of the above compounds, pharmaceutical compositions which contain such compounds as well as the use of these compounds in the treatment of inflammatory conditions.
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- Bicyclic imidazolyl derivatives as phosphodiesterase inhibitors, pharmaceutical compositions and method of use
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The present invention provides for compounds having the following Formulae I-III, and The compounds of the present invention are useful in the treatment of a variety of disease such as glaucoma, sexual dysfunction, asthma and cardiovascular disorders such as stable-, unstable- and variant-angina, hypertension, pulmonary hypertension, congestive heart failure, atherosclerosis, and thrombosis.
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- Scavenger assisted combinatorial process for preparing libraries of tertiary amine compounds
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This invention relates to a novel solution phase process for the preparation of tertiary amine combinatorial libraries. These libraries have utility for drug discovery and are used to form wellplate components of novel assay kits.
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- 3-AMINOAZEPINE COMPOUND AND PHARMACEUTICAL USE THEREOF
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A 3-aminoazepine compound represented by general formula (I), an optically active isomer thereof, or a pharmaceutically acceptable salt thereof, wherein Ar represents phenyl, etc.; R1 represents hydrogen, alkyl, etc.; R2 and R3 represent each independently hydrogen, alkyl,-CO-R? (wherein R? represents heteroaryl, etc.),-CONH-R? (wherein R? represents phenyl, etc.), etc.; R? represents hydrogen, alkyl, etc.; X represents oxygen or sulfur, provided R? and X may be combined together to form-C(R1?)=N-N= (wherein R1? represents hydrogen, alkyl, etc.). This compound has CCK and gastrin antagonisms and is useful as a remedy for central nervous system diseases such as anxiety and depression and as a preventive or a remedy for pancreatic diseases and gastrointestinal ulcer.
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- An Intramolecular Element Effect in Nucleophilic Vimylic Substitution Reactions
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Fluorochloro- and fluorobromoethenes CHX=CFX (X = Cl, Br) in reactions with sodium alkoxides RONa (R = Me, Et, i-Pr, t-Bu) in the corresponding alcohols afford the products of monosubstitution of both chlorine (bromine) and fluorine, as well as orthoesters XCH2C(OR)3 and esters XCH2COOR. The stereochemistry of the reactions and the intramolecular element effect are discussed.
- Shainyan,Danilevich
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p. 188 - 192
(2007/10/03)
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- Synthesis and characterization of all-E (12,12'-13C2)-, (13,13'-13C2)-, (14,14'-13C2)-, (15,15'-13C2)- and (20,20'-13C2)astaxanthin
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The all-E isomers of (12,12'-13C2)-, (13,13'-13C2)-, (14,14'-13C2)-, (15,15'-13C2)- and (20,20'-13C2)astaxanthin were prepared by total synthesis starting from commercially available 99percent 13C-enriched acetonitrile, acetic acid and methyl iodide.The astaxanthins were obtained in high purity and with high isotope incorporation (>99percent for every position).For this synthesis, the C15 + C10 + C15 strategy was used.The central C10-synthon, 2,7-dimethylocta-2,4,6-triene-1,8-dial, was symmetrically dilabelled at any position using two new synthetic schemes.The 13C2-enriched C10-dialdehydes were then converted in one step to the 13C2-enriched astaxanthins.
- Jansen, F. J. H. M.,Kwestro, M.,Schmitt, D.,Lugtenburg, J.
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p. 552 - 562
(2007/10/02)
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- Pesticidal compounds
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The present invention provides a class of novel substituted bicyclooctanes which have pesticidal activity, particularly against arthropod pests. Pesticidal formulations containing the compounds of the formula (I), their use in the control of pests and methods for their preparation are also disclosed.
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- Carboxylic acid derivatives and pharmaceutical compositions and uses
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The present invention provides carboxylic acid derivatives of the general formula: STR1 wherein R1 and R2, which can be the same or different, are optionally substituted aryl radicals or optionally substituted heterocyclic radicals, A is a straight-chained or branched, saturated or unsaturated alkylene chain containing up to 10 carbon atoms which can contain an oxygen, sulphur or nitrogen atom and is optionally substituted by a hydroxyl group, Y is an S(O)n group or an oxygen atom, n is 0, 1 or 2 and B is a valency bond or a saturated or unsaturated alkylene radical containing up to 5 carbon atoms; as well as the physiologically acceptable salts, esters and amides thereof, with the proviso that (a) R1 and R2 are not simultaneously aryl radicals and (b) when an unsaturated alkylene chain is present which contains a heteroatom, the heteroatom is not connected to an unsaturated aliphatic carbon atom. The present invention also provides processes for the preparation of these new compounds and pharmaceutical compositions containing them.
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- Syntheses and Reactions of Optically Active Alkyltoluene-p-sulphinamides. Part 2. Substitution at Sulphur with Retention of Configuration
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The stereochemistry of the reaction of optically active sulphonamides (1a-c) with different alkylating agents has been examined.The electrophilic attack on sulphoximidate anions occurs only at nitrogen.Prevailing retention of configuration at sulphur (e.e. up to 48percent) is observed in the formation of p-tolylsulphinyl acetates from sulphinamides (1b-c) with α-bromo esters.
- Colonna, Stefano,Germinario, Giulio,Manfredi, Amedea,Stirling, Charles, J. M.
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p. 1695 - 1698
(2007/10/02)
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- Furoxanthone derivatives useful as diuretics
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Xanthone derivatives of the formula (I): STR1 (wherein W, X, Y and Z which may be the same or different represent a hydrogen atom, a halogen atom or a lower alkyl group having 1 to 4 carbon atoms; A is hydrogen atom or together with Z forms a --CH2 -- group which binds to a phenyl carbon adjacent the phenyl carbon to which the oxygen of the group STR2 is attached to form a cyclic methylene chain; B is a hydroxymethyl group, a lower alkoxycarbonyl group having 1 to 4 carbon atoms, or a carboxyl group, provided that W is neither a hydrogen atom nor a 7-position methyl group when X, Y and Z are each a hydrogen atom, and A is a hydrogen atom and B is a carboxyl group or a lower alkoxycarbonyl group), as well as non-toxic salts thereof when B is a carboxyl group, and a process for preparing the same are disclosed. The compounds of formula (I) in accordance with the present invention are useful as diuretics having uricosuric activity and can be used in the treatment of edema or hypertension.
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- STEREOSPECIFIC DISPLACEMENT OF SULFUR FROM CHIRAL CENTERS. ACTIVATION VIA THIAPHOSPHONIUM SALTS.
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The first general method for direct displacement of sulfur from chiral carbon centers has been developed.Chiral mercaptans are readily converted to the corresponding thiaphosphonium salts by treatment with t-butyl hypochlorite and hexamethylphosphorous triamide.Metathesis with ammonium hexafluorophosphate provides stable, isolable, crystalline salts which undergo clean nucleophilic diplacement with a variety of heteroatom and carbon based nucleophiles, affording products in which the stereochemistry has been inverted.
- Krafft, Grant A.,Siddall, Thomas L.
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p. 4867 - 4870
(2007/10/02)
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- Highly Effective Catalytic Methods for Ylide Generation from Diazo Compounds. Mechanism of the Rhodium- and Copper-Catalyzed Reactions with Allylic Compounds
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The catalytic effectiveness of rhodium(II) acetate and hexadecacarbonylhexarhodium for ylide generation in reactions of diazo compounds with allyl methyl sulfide, representative allylic tertiary amines, and allyl halides is described.Exclusive formation of products derived from the sigmatropic rearrangement of ylide intermediates generated from ethyl diazoacetate and allyl sulfides, amines, or iodides is observed.Cyclopropanation is dominant in reactions of either diethyl diazomalonate or ethyl diazoacetate with allyl chloride, and competition between cyclopropanation and ylide rearrangement is exhibited in reactions with allyl bromide.Allyl iodide and allyl methyl sulfide are very similar in their ability to intercept the presumed carbenoid intermediates.Copper catalysis results in significantly higher yields of ylide-derived products, relative to cyclopropane products, than does rhodium catalysis in reactions with allyl bromides and chlorides.Reactions with crotyl bromide further exemplify the catalytic dissimilarities of rhodium and copper compounds and identify alternative transformations of metal-associated ylide intermediates.Cyclopropanation and metal ylide formation are represented as competing processes.Metal dissociation from the metal-associated ylide intermediate produces a reactive allylic ylide that is subject to the sigmatropic rearrangement.However, products derived from rearrangement of the metal-associated ylide by allyl group transfer to the metal are observed to predominate in copper-catalyzed reactions of ethyl diazoacetate with crotyl bromide.These same products are not observed in rhodium(II) acetate catalyzed reactions performed at or below 25 deg C.
- Doyle, Michael P.,Tamblyn, William H.,Bagheri, Vahid
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p. 5094 - 5102
(2007/10/02)
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